Table 1.
HR of residual glucose variability for nephropathy
| Measure of glycaemic variability | Model 1 (age adjustment) |
Model 2a
(multivariate adjustment) |
Model 3b
(Model 2 + cumul. average HbA1c) |
|||
|---|---|---|---|---|---|---|
| HR (95% CI) | p value | HR (95% CI) | p value | HR (95% CI) | p value | |
| UKPDS (n=4185) | ||||||
| RSD | 1.49 (0.90, 2.49) | 0.120 | 1.86 (1.07, 3.26) | 0.027 | 1.74 (0.84, 3.61) | 0.133 |
| RARV | 1.39 (0.83, 2.30) | 0.219 | 1.71 (0.99, 2.96) | 0.056 | 1.66 (0.81, 3.44) | 0.168 |
| ACCORD (n=9930) | ||||||
| RSD | 1.56 (1.39, 1.76) | <0.0001 | 1.46 (1.29, 1.67) | <0.0001 | 1.37 (1.18, 1.59) | <0.0001 |
| RARV | 1.40 (1.29, 1.54) | <0.0001 | 1.34 (1.21, 1.50) | <0.0001 | 1.27 (1.13, 1.43) | <0.0001 |
| VADT (n=1606) | ||||||
| RSD | 1.86 (1.50, 2.30) | <0.0001 | 1.54 (1.23, 1.93) | <0.0001 | 1.57 (1.22, 2.03) | 0.002 |
| RARV | 1.66 (1.41, 1.97) | <0.0001 | 1.45 (1.20, 1.74) | <0.0001 | 1.47 (1.19, 1.80) | 0.001 |
| Meta-analysisc (n=15,753) | ||||||
| RSD | 1.61 (1.46, 1.79) | <0.0001 | 1.49 (1.33, 1.66) | <0.0001 | 1.40 (1.24, 1.59) | <0.0001 |
| RARV | 1.45 (1.35, 1.58) | <0.0001 | 1.37 (1.25, 1.50) | <0.0001 | 1.31 (1.18, 1.44) | <0.0001 |
eGFR was generated from the Modification of Diet in Renal Disease Study (MDRD) equation for each study. Nephropathy was defined as eGFR <45 ml min−1 [1.73 m]−2
Model 2: in each study, Model 2 is adjusted for all covariates that significantly differed between those with and without nephropathy during the study (ESM Table 1). In UKPDS, in addition to baseline age, we additionally adjusted for: baseline diastolic blood pressure (DBP), systolic blood pressure (SBP), LDL, total cholesterol, baseline eGFR, Early Treatment Diabetic Retinopathy Study (ETDRS) test score prior to randomisation, and sex. In ACCORD, in addition to baseline age, we additionally adjusted for: duration of diabetes, baseline DBP, SBP, HDL, total cholesterol, eGFR, sex, race, CVD history, and history of heart failure and eye disease. In VADT, we additionally adjusted for diabetes duration, SBP, DBP, baseline eGFR, and history of CVD and eye disease. Note: since eGFR was estimated using creatine levels, we did not adjust for albumin/creatinine ratio (ACR) even though it was a significantly different covariate between those with and without nephropathy (ESM Table 2 and ESM Table 3)
Model 3: additionally, adjusted for cumulative (cumul.) average of HbA1c as well as the covariates adjusted for in Model 2
A fixed-effect inverse variance meta-analysis was adopted and Q heterogeneity statistics were all non-significant (>0.05) (a random-effect meta-analysis yielded very similar results)